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Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation

Moshikur, R.M. and Chowdhury, M.R. and Wakabayashi, R. and Tahara, Y. and Moniruzzaman, M. and Goto, M. (2019) Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation. Journal of Molecular Liquids, 278 . pp. 226-233.

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Abstract

The technological utility of active pharmaceutical ingredients (APIs) is enormously improved when they are converted into ionic liquids (ILs). API-ILs possess better aqueous solubility and thermal stability than that of solid-state salt or crystalline drugs. However, many such API-ILs are not biocompatible or biodegradable. In the current study, we synthesized a series of IL-APIs using methotrexate (MTX), a potential anticancer prodrug, and biocompatible IL-forming cations (choline and amino acid esters). The MTX-IL moieties were characterized through 1 H NMR, FTIR, p-XRD, DSC and thermogravimetric analysis. The solubility of the MTX-ILs was evaluated in simulated body fluids (phosphate-buffered saline, simulated gastric, and simulated intestinal fluids). An assessment of the in vitro antitumor activity of the MTX-ILs in a mammalian cell line (HeLa cells) was used to evaluate their cytotoxicity. The MTX-ILs showed aqueous solubility at least 5000 times higher than that of free MTX and two orders of magnitude higher compared with that of a sodium salt of MTX in both water and simulated body fluids. Importantly, a proline ethyl ester MTX prodrug showed similar solubility as the MTX sodium salt but it provided improved in vitro antitumor activity. These results clearly suggest that the newly synthesized API-ILs represent promising potential drug formulations. © 2019 Elsevier B.V.

Item Type:Article
Impact Factor:cited By 0
Uncontrolled Keywords:Biocompatibility; Body fluids; Cell culture; Cytotoxicity; Drug products; Esters; Ionic liquids; Lanthanum compounds; Mammals; Salts; Sodium; Solubility; Thermogravimetric analysis, Active pharmaceutical ingredients; Mammalian cell lines; Methotrexate; Methotrexate (MTX); Orders of magnitude; Phosphate-buffered salines; Simulated body fluids; Technological utility, Drug delivery
ID Code:22113
Deposited By: Ahmad Suhairi
Deposited On:28 Feb 2019 08:02
Last Modified:28 Feb 2019 08:02

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